Complete genome sequence of Treponema paraluiscuniculi, strain Cuniculi A: the loss of infectivity to humans is associated with genome decay

Abstract

Treponema paraluiscuniculi is the causative agent of rabbit venereal spirochetosis. It is not infectious to humans, although its genome structure is very closely related to other pathogenic Treponema species including Treponema pallidum subspecies pallidum, the etiological agent of syphilis. In this study, the genome sequence of Treponema paraluiscuniculi, strain Cuniculi A, was determined by a combination of several high-throughput sequencing strategies. Whereas the overall size (1,133,390 bp), arrangement, and gene content of the Cuniculi A genome closely resembled those of the T. pallidum genome, the T. paraluiscuniculi genome contained a markedly higher number of pseudogenes and gene fragments (51). In addition to pseudogenes, 33 divergent genes were also found in the T. paraluiscuniculi genome. A set of 32 (out of 84) affected genes encoded proteins of known or predicted function in the Nichols genome. These proteins included virulence factors, gene regulators and components of DNA repair and recombination. The majority (52 or 61.9%) of the Cuniculi A pseudogenes and divergent genes were of unknown function. Our results indicate that T. paraluiscuniculi has evolved from a T. pallidum-like ancestor and adapted to a specialized host-associated niche (rabbits) during loss of infectivity to humans. The genes that are inactivated or altered in T. paraluiscuniculi are candidates for virulence factors important in the infectivity and pathogenesis of T. pallidum subspecies.

Figure 1. A schematic representation of tpr genes in the Cuniculi A and Nichols genomes.

Identities at nucleotide levels of Cuniculi A and Nichols genomes are shown. Colors indicate sequence similarities among paralogous tpr genes, i.e. sequence similarities within the T. paraluiscuniculi genome (e.g. tprC and tprD genes are identical). In the Cuniculi A genome, reverted frameshift mutation (in tprA), frameshift mutations (in tprC,D,E,F,G,J,K), deletions (in tprF,G,I) and gene elongation are present (in tprL). The tprF deletion shown in the Nichols genome is based on the tprF sequence taken from T. pallidum ssp. pertenue Samoa D genome (data not shown). In the Cuniculi A and Nichols tprK genes, shorter gene versions (starting with the next available downstream start codon) are expected rather than the presence of frameshift mutation in the Cuniculi A tprK.